The ability of chronic lithium administration to modify tricyclic antidepressant-induced supersensitivity development in cells receiving 5-hydroxytryptamine input was investigated using microiontophoretic and single-cell recording techniques. Chronic tricyclic antidepressant administration for a period of 14 days resulted in a 5-fold increase in the sensitivity of hippocampal pyramidal cells to iontophoretically applied 5-hydroxytryptamine. This supersensitivity was not blocked by the concurrent administration of lithium.